Depression and Comorbid Cardiovascular Disease

It is important to understand the interplay of medical and psychiatric disorders. Charles B. Nemeroff, MD, PhD, Reunette W. Harris Professor and Chairman, Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, offered a review of the relationships between cardiovascular disease and depressive disorders at this year’s American Psychiatric Association annual meeting.

Depression

Depression is the most common psychological problem in the US. Minor Depression can be attributed to normal depressed feelings that arise because of a specific life situation, a side effect of medication, hormonal changes or physical illness, and does not usually require treatment. Major Depression (depressive illness) is a serious condition that result in extreme fatigue, sleep problems and eventually an inability to function. The exact cause is unknown, but it is thought to be a malfunction of brain neurotransmitters, which are chemicals that modulate moods. Major Depression is usually treated with a combination of psychotherapy and antidepressants which moderate or correct chemical imbalances in the brain. The group of antidepressants most frequently prescribed is the selective serotonin reuptake inhibitors (SSRIs) which regulate the neurotransmitter serotonin.

Examples:
Amitriptyline HCL
WELLBUTRIN
Wellbutrin SR
Fluoxetine
Celexa
Lexapro
Paxil
Prozac
Remeron
Zoloft
Effexor XR

Several large studies have now demonstrated a relationship between depression and ischemic heart disease (IHD).

A study by Anda and colleagues followed more than 2800 participants for a mean of 12.4 years and demonstrated that patients with depressed affect and/or moderate/severe hopelessness, as assessed by a general well-being schedule given during their initial baseline assessment, had a much higher risk for both fatal and nonfatal IHD. This study clearly suggested that depressive-like symptomatology may be a risk factor for the subsequent development of IHD. Depression is also very common in patients with coronary artery disease (CAD). Approximately 23% of patients met Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for depression in a study by Gonzalez and colleagues. In this study, both family history of psychopathology and the severity of medical illness were significant predictions of depression.

In another study, patients who met DSM-III-R criteria for depression 7 days after a myocardial infarction (MI) were also assessed both 6 months and 18 months after an acute MI. The rate of coronary deaths among the nondepressed patients (n = 187) was approximately 3% at 6 months and 6% at 18 months. Among the depressed patients (n = 35), the incidence of coronary death was approximately 16.5% at 6 months and 20% at 18 months, demonstrating that depression particularly increased the rate of coronary death within 6 months of the initial MI. The results from the Baltimore ECA follow-up study also determined the role of major depression as a risk factor for MI and factored in the involvement of psychotropic medications. This study demonstrated that depression increased the risk of developing an MI by 4.54, and even dysphoria increased the odds ratio for developing an MI by over 2-fold. This study also demonstrated barbiturates, phenothiazines, and lithium were associated with an increased MI risk. whereas tricyclic antidepressants (TCAs) were not. A number of large prospective studies in patients without CAD upon study entry have now demonstrated that depression is a significant independent risk factor for CAD, with an adjusted relative risk in the range of 1.5- to 2-fold, which is similar to tobacco and smoking.

There are several possible mechanisms that may underlie the increased propensity for IHD in patients with depression. Depression is associated with a number of alterations, including hyperactivity of the hypothalamic-pituitary (HPA) axis and increased sympathetic activity. There is also evidence suggesting elevated secretion of cytokines, which are powerful mediators of the immune system. Functional abnormalities in platelet function have received particular attention, as they are one of the key mediators of clot formation. It is also notable that platelets have neuroectodermal origin and so are of the same lineage as central serotonergic neurons.

A small study by Musselman and colleagues, which measured a number of markers related to platelet activation, showed exaggerated platelet reactivity in patients with major depression. A study by Pollock and colleagues also demonstrated increased platelet activation in patients with IHD and depression. Of particular interest, treatment with paroxetine (a selective serotonin reuptake inhibitor [SSRI]) but not nortriptyline (primarily a norepinephrine reuptake inhibitor) reduced measures of platelet reactivity in this study. Agents that target serotonin may be particularly effective, as serotonin is directly involved in platelet activation and has antiplatelet activity, which may be demonstrated by the frequent occurrence of bruises in patients taking SSRIs. Several studies have also demonstrated SSRIs are effective in reducing platelet activation in depressed patients.

Independent of increased platelet reactivity, depression has also been associated with reduced heart rate variability, a known predictor for poor outcome in CAD. Dr. Nemeroff highlighted the fact that tricyclic drugs are particularly dangerous in patients with heart disease, as they reduce heart rate variability. Reductions in heart rate variability may result in heart failure, conduction abnormalities or arrhythmia in the diseased heart (although they may produce only orthostatic hypotension in a healthy heart).

A large study was undertaken (the SADHART trial) to evaluate the cardiovascular safety, tolerability, and antidepressant efficacy of sertraline treatment in patients with an acute MI or unstable angina. Overall, this study demonstrated sertraline to be safe and effective in this population. Although sertraline did not significantly lower the development of adverse cardiovascular events relative to placebo, most measures showed improvements in the sertraline group. It is likely that this study was underpowered; of the more than 11,500 patients interviewed, only 369 patients successfully completed the study. Overall, some compelling evidence was presented suggesting depression is an independent risk factor for the development of IHD, and that SSRIs may be particularly effective in reducing the incidence of adverse cardiovascular events in these patients.

Provided by ArmMed Media
Revision date: July 9, 2011
Last revised: by Sebastian Scheller, MD, ScD